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Treatment for Angelman syndrome (AS) is currently limited to symptomatic interventions. A mouse model of AS has reduced calcium/calmodulin-dependent kinase II activity due to excessive phosphorylation of specific threonine residues, leading to diminished long-term potentiation. In a rat model of Parkinson disease, levodopa reduced phosphorylation of various proteins, including calcium/calmodulin-dependent kinase II. Further studies demonstrated that AS mice treated with levodopa performed better on rotarod testing than untreated AS mice. We conducted a multi-center double-blind randomized placebo-controlled 1-year trial of levodopa / carbidopa with either 10 or 15 mg/kg/day of levodopa in children with AS. The outcome of this intervention was assessed using either the Bayley Scales of Infant Development or the Mullen Scales of Early Learning, as well as the Vineland Adaptive Behavior Scales, and the Aberrant Behavior Checklist. Of the 78 participants enrolled, 67 participants received study medication (33 on levodopa, 34 on placebo), and 55 participants (29 on levodopa, 26 on placebo) completed the 1-year study. There were no clinically or statistically significant changes in any of the outcome measures over a 1-year period comparing the levodopa and placebo groups. The number of adverse events reported, including the more serious adverse events, was similar in both groups, but none were related to treatment with levodopa. Our data demonstrate that levodopa is well-tolerated by children with AS. However, in the doses used in this study, it failed to improve their neurodevelopment or behavioral outcome.
Asunto(s)
Síndrome de Angelman/tratamiento farmacológico , Levodopa/uso terapéutico , Síndrome de Angelman/diagnóstico , Síndrome de Angelman/fisiopatología , Síndrome de Angelman/psicología , Animales , Biomarcadores , Calcio/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Modelos Animales de Enfermedad , Humanos , Levodopa/administración & dosificación , Potenciación a Largo Plazo , Ratones , Pruebas Neuropsicológicas , Resultado del TratamientoRESUMEN
BACKGROUND: Kendo, a martial art developed by the samurai, is rooted deep in Japanese culture with traditional armor that has seen little change over the past centuries. Despite its century-old design, kendo helmets are manufactured without third-party testing to verify their quality and effectiveness against head trauma. OBJECTIVE: To evaluate the effectiveness of different helmet stitching patterns and padding materials in mitigating impact forces that could lead to sports-related concussions (SRC) in kendo, and to assess variations in safety performance across different genders and kendo ranks (Dan and Kyu). METHODS: We collected data from 10 kendo practitioners (six males and four females), analyzing over 4,000 strikes using shinai on a sensor-equipped mannequin. Various helmet stitching patterns (ranging from 2 mm to 9 mm) and padding types (polyurethane-based and different thicknesses of cotton-based pads) were tested under controlled conditions simulating realistic impacts encountered in kendo practice. RESULTS: The results indicated that helmets with wider stitching patterns (e.g. 8 mm and 9 mm) generally offered better energy absorption, exhibiting statistically significant lower mean g-forces with a 95% confidence interval compared to tighter patterns (2 mm, 4 mm, 6 mm, and 8 mm x 2 mm) (p < 0.001). Additionally, the polyurethane-based padding outperformed cotton-based padding by a statistically significant reduction of impact force (p < 0.001). Significant differences in striking force were also observed between genders and ranks, with male and higher-rank (Dan) practitioners delivering stronger impacts (both p < 0.001). CONCLUSIONS: This study highlights the critical influence of helmet stitching patterns and padding materials on the protective capabilities against concussions in kendo. Even though helmets with narrower stitching patterns cost more, helmets with wider stitching patterns and polyurethane padding material provide enhanced safety benefits. We do not know how the difference in striking force between genders and ranks affects the outcome of a kendo match.
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OBJECTIVES AND DESIGN: Information about providing professional and appropriate perinatal care to transgender men in the perinatal setting is scarce, and healthcare providers often have insufficient knowledge or skills to provide this care. In response, a quality improvement educational program for nursing staff was developed and implemented, with the goal of evaluating the impact of this intervention on nurses' knowledge, skills, and attitudes when caring for pregnant transgender men. SETTING AND PARTICIPANTS: The training was offered to nursing staff of a 24-bed inpatient perinatal unit at a large, private academic medical center in a major East Coast city during the unit's quarterly staff meeting in March 2020. INTERVENTION: The training covered the provision of affirming and inclusive perinatal care for transgender men. The content of the training was based on recommendations in the literature and reviewed by content experts. MEASUREMENTS: Pre-test (N = 55) and post-test (N = 23) online self-administered surveys assessed nursing staff's knowledge of, comfort, and interest in providing gender affirming care for transgender men. Mann-Whitney U and Fischer's exact tests were used to determine significant changes in knowledge and attitudes over time. FINDINGS: Findings suggest the training improved nursing staff's self-reported knowledge and skills in providing gender affirming care to pregnant transgender men over time, with participants demonstrating improved knowledge about communication around pronouns, gender identity, reproductive systems, and obstetric history. Awareness of resources for both professional development and to refer transgender patients also improved. However, persistent deficits in other knowledge, skills, and attitudes remained, suggesting that nurses would likely benefit from further support and training in transgender-specific health issues. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Findings support the utility of unit-based training in improving affirming and inclusive care in the perinatal setting. This highlights opportunities for supporting nurses' professional practice of caring for transgender patients experiencing pregnancy and may be adapted for use in other specialty units.
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Enfermeras y Enfermeros , Personas Transgénero , Embarazo , Humanos , Femenino , Masculino , Identidad de Género , Competencia Clínica , Personal de Salud/educaciónRESUMEN
IMPORTANCE: COVID-19 has adversely affected global healthcare infrastructure since 2019. Currently, there are no large-scale published reports on the efficacy of combination therapy of dexamethasone, remdesivir, and tocilizumab on COVID-19 patients. OBJECTIVES: Is the combination therapy of dexamethasone, remdesivir, and tocilizumab superior to other treatments on hospitalized COVID-19 patients? DESIGN: This is a retrospective, comparative effectiveness study. SETTING: Single-center study PARTICIPANTS/INTERVENTIONS: We analyzed different inpatient COVID-19 treatment options available in the United States and their impact on hospital length of stay (LOS) and mortality. Hospitalized COVID-19 were categorized as "mild," "moderate" and "severe'' based on the highest level of oxygen required; room air, nasal cannula, or high flow/PAP/intubation, respectively. Patients were treated in accordance with the availability of medications and the latest treatment guidelines. MAIN OUTCOMES: The endpoints of the study are hospital discharges and death during hospitalization. RESULTS: 1233 COVID-19 patients were admitted from 2020 to 2021. No treatment combinations showed a statistically significant decrease in hospital LOS in mild COVID-19 patients (p = 0.186). In moderate patients, the combination of remdesivir and dexamethasone slightly decreased LOS by 1 day (p = 0.007). In severe patients, the three-drug combination of remdesivir, dexamethasone, and tocilizumab decreased LOS by 8 days (p = 0.0034) when compared to nonviable treatments, such as hydroxychloroquine and convalescent plasma transfusion. However, it did not show any statistically significant benefit when compared to two-drug regimens (dexamethasone plus remdesivir) in severe COVID-19 (p = 0.116). No treatment arm appeared to show a statistically significant decrease in mortality for severe COVID-19 patients. CONCLUSIONS: Our findings suggest that three-drug combination may decrease LOS in severe COVID-19 patients when compared to two-drug therapy. However, the trend was not supported by statistical analysis. Remdesivir may not be clinically beneficial for mild hospitalized COVID-19 patients; considering its cost, one could reserve it for moderate and severe patients. Triple drug therapies, while potentially reducing LOS for severe patients, do not affect overall mortality. Additional patient data may increase statistical power and solidify these findings.
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COVID-19 , Humanos , COVID-19/terapia , Tiempo de Internación , SARS-CoV-2 , Tratamiento Farmacológico de COVID-19 , Estudios Retrospectivos , Transfusión de Componentes Sanguíneos , Resultado del Tratamiento , Sueroterapia para COVID-19 , Plasma , Dexametasona/uso terapéutico , HospitalesRESUMEN
OBJECTIVE: to examine the usage and content of the Global Alliance for Nursing and Midwifery (GANM) discussion forum in relation to nursing and midwifery education and practice. METHOD: a qualitative conventional content analysis was performed. Subject lines from 1689 discussion board threads were extracted and used as the unit of analysis. A-priori codes were developed based on topical relevance (e.g. maternal health) and typical discussion board usage (e.g. announcing educational opportunities). Emerging codes were further identified while coding the data (e.g. infectious diseases). RESULTS: the GANM discussion forum was used most frequently for information exchange (43.8%), such as dissemination of new information on evidence-based practice, and to announce educational opportunities (24.8%). The most frequently discussed topics were nursing (14.2%; e.g. the role of nurses in primary care, nursing education, etc.) and maternal health (13.8%; e.g. postpartum care, maternal mortality, etc.). Infectious diseases were discussed in 9% of threads, 40% of which concerned the current coronavirus pandemic. CONCLUSION: findings reinforce the utility of the GANM as a platform for professional development and continuing education. As a platform for disseminating empirical research, the GANM can be leveraged to have an influence on real-world, evidence-based practice.
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Educación en Enfermería , Partería , Femenino , Humanos , EmbarazoRESUMEN
Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. Disturbed glutamate signaling resulting in hypofunction of N-methyl-D-aspartate receptors (NMDAR) has been implicated in the pathophysiology of schizophrenia. Glutamate Carboxypeptidase II (GCP II) hydrolyzes N-acetyl-alpha L-aspartyl-L-glutamate (NAAG) into glutamate and N-acetyl-aspartate. NAAG is a neuropeptide that is an NMDAR antagonist as well as an agonist for the metabotropic glutamate receptor-3 (mGluR3), which inhibits glutamate release. The aggregate effect of NAAG is thus to attenuate NMDAR activation. To manipulate the expression of GCP II, LoxP sites were inserted flanking exons 1 and 2, which were excised by crossing with a Cre-expressing mouse. The mice heterozygous for this deletion showed a 50% reduction in the expression level of protein and functional activity of GCP II in brain samples. Heterozygous mutant crosses did not yield any homozygous null animals at birth or as embryos (N > 200 live births and fetuses). These data are consistent with the previous report that GCP II homozygous mutant mice generated by removing exons 9 and 10 of GCP II gene were embryonically lethal and confirm our hypothesis that GCP II plays an essential role early in embryonic development. Heterozygous mice, however, developed normally to adulthood and exhibited increased locomotor activity, reduced social interaction, and a subtle cognitive deficit in working memory.
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Glutamato Carboxipeptidasa II/deficiencia , Heterocigoto , Mutación/genética , Fenotipo , Estimulación Acústica/métodos , Animales , Conducta Animal/fisiología , Exones/genética , Expresión Génica/genética , Glutamato Carboxipeptidasa II/genética , Glutamato Carboxipeptidasa II/metabolismo , Relaciones Interpersonales , Memoria/fisiología , Ratones , Ratones Noqueados , Actividad Motora/genética , Receptores de Glutamato Metabotrópico/genética , Receptores de Glutamato Metabotrópico/metabolismo , Filtrado Sensorial/genética , Percepción Espacial/fisiologíaRESUMEN
Adenosine A2A receptor (A2AR) agonists have been shown to decrease tissue inflammation induced by hypoxia/reoxygenation in mice with sickle cell disease (SCD). The key mediator of the A2AR agonist's anti-inflammatory effects is a minor lymphocyte subset, invariant natural killer T (iNKT) cells. We tested the hypothesis that administration of an A2AR agonist in patients with SCD would decrease iNKT cell activation and dampen the severity of vaso-occlusive (VO) crises. In a phase 2, randomized, placebo-controlled trial, we administered a 48-hour infusion of the A2AR agonist regadenoson (1.44 µg/kg per hour) to patients with SCD during VO crises to produce a plasma concentration of â¼5 nM, a concentration known from prior studies to suppress iNKT cell activation in SCD. The primary outcome measure was a >30% reduction in the percentage of activated iNKT cells. Ninety-two patients with SCD were randomized to receive a 48-hour infusion of regadenoson or placebo, in addition to standard-of-care treatment, during hospital admission for a VO crisis and had analyzable iNKT cell samples. The proportion of subjects who demonstrated a reduction of >30% in activated iNKT cells was not significantly different between the regadenoson and placebo arms (43% vs 23%; P = .07). There were also no differences between regadenoson and placebo groups in length of hospital stay, mean total opioid use, or pain scores. These data demonstrate that a low-dose infusion of regadenoson intended to reduce the activity of iNKT cells is not sufficient to produce a statistically significant reduction in such activation or in measures of clinical efficacy. This trial was registered at www.clinicaltrials.gov as #NCT01788631.
RESUMEN
Objective: to examine the usage and content of the Global Alliance for Nursing and Midwifery (GANM) discussion forum in relation to nursing and midwifery education and practice. Method: a qualitative conventional content analysis was performed. Subject lines from 1689 discussion board threads were extracted and used as the unit of analysis. A-priori codes were developed based on topical relevance (e.g. maternal health) and typical discussion board usage (e.g. announcing educational opportunities). Emerging codes were further identified while coding the data (e.g. infectious diseases). Results: the GANM discussion forum was used most frequently for information exchange (43.8%), such as dissemination of new information on evidence-based practice, and to announce educational opportunities (24.8%). The most frequently discussed topics were nursing (14.2%; e.g. the role of nurses in primary care, nursing education, etc.) and maternal health (13.8%; e.g. postpartum care, maternal mortality, etc.). Infectious diseases were discussed in 9% of threads, 40% of which concerned the current coronavirus pandemic. Conclusion: findings reinforce the utility of the GANM as a platform for professional development and continuing education. As a platform for disseminating empirical research, the GANM can be leveraged to have an influence on real-world, evidence-based practice.
Objetivo: examinar o uso e o conteúdo do fórum de discussão da Aliança Global para Enfermagem e Obstetrícia (Global Alliance for Nursing and Midwifery, GANM) em relação à educação e prática de enfermagem e obstetrícia. Método: análise de conteúdo convencional qualitativa. Foram extraídas e usadas como unidade de análise linhas de assunto de 1.689 tópicos do fórum de discussão. A priori, os códigos foram desenvolvidos com base na relevância do tópico (por exemplo, saúde materna) e no uso típico de um fórum de discussão (por exemplo, anúncio de oportunidades educacionais). Códigos emergentes foram identificados posteriormente durante a codificação dos dados (por exemplo, doenças infecciosas). Resultados: o fórum de discussão da GANM foi utilizado com maior frequência para troca de informações (43,8%), como divulgação de novas informações sobre a prática baseada em evidências e para anunciar oportunidades educacionais (24,8%). Os tópicos mais discutidos foram Enfermagem (14,2%; por exemplo, o papel do enfermeiro na atenção primária, educação em enfermagem, etc.) e saúde materna (13,8%; por exemplo, cuidados pósparto, mortalidade materna, etc.). Doenças infecciosas foram discutidas em 9% dos tópicos, sendo que 40% estavam relacionados à atual pandemia de coronavírus. Conclusão: os achados reforçam a utilidade da GANM como plataforma de desenvolvimento profissional e educação continuada. Como plataforma para disseminar a pesquisa empírica, a GANM pode ser aproveitada para ter uma influência na prática do mundo real baseada em evidências.
Objetivo: examinar el uso y contenido del foro de discusión de la Alianza Global para Enfermería y Obstetricia (Global Alliance for Nursing and Midwifery, GANM) en relación con la educación y práctica de Enfermería y Obstetricia. Método: se realizó un análisis de contenido convencional cualitativo. Se extrajeron líneas de 1689 hilos de conversación en foros de discusión y se utilizaron como unidad de análisis. A priori, los códigos se desarrollaron sobre la base de la relevancia del tema (por ejemplo, salud materna) y el uso típico de los foros de discusión (por ejemplo, anunciar oportunidades educativas). Los códigos emergentes se identificaron con mayor precisión al codificar los datos (por ejemplo, enfermedades infecciosas). Resultados: el foro de discusión de la GANM se utilizó con mayor frecuencia para el intercambio de información (43,8%), como la difusión de nueva información sobre la práctica basada en la evidencia, y para anunciar oportunidades educativas (24,8%). Los temas más discutidos fueron la Enfermería (14,2%; por ejemplo, el rol de los enfermeros en la atención primaria, educación en Enfermería, etc.) y la salud materna (13,8%; por ejemplo, atención postparto, mortalidad materna, etc.). Las enfermedades infecciosas se discutieron en 9% de los hilos de conversación, de los cuales, el 40% refirieron a la actual pandemia de coronavirus. Conclusión: los hallazgos refuerzan la utilidad de la GANM como plataforma para el desarrollo profesional y la educación continua. Como plataforma para difundir investigación empírica, la GANM se puede aprovechar para influir en la práctica basada en la evidencia del mundo real.